School of Life Sciences, Tianjin University, Tianjin Engineering Center of Micro Nano Biomaterials and Detection Treatment Technology, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin, 300072, China.
Key Laboratory of Analytical Science and Technology of Hebei Province, College of Chemistry and Environmental Science, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University, Baoding, 071002, China.
Biomaterials. 2021 Feb;269:120654. doi: 10.1016/j.biomaterials.2021.120654. Epub 2021 Jan 5.
A variety of therapies have been developed and used for the treatment of colon cancer, however, the high mortality rate remains high and more effective strategies are still in urgent needs. In this study, an immunotherapy approach that is composed of innate immune activator Astragaloside III (As) and the photodynamic therapy (PDT) reagent chlorine e6 (Ce6) ((As + Ce6)@MSNs-PEG), was developed for colon cancer treatment. We showed that (As + Ce6)@MSNs-PEG could effectively activate NK cells and inhibit the proliferation of tumor cells in vitro. It could also effectively reach tumor sites, induce infiltration of immune cells into the tumor, and enhance the cytotoxicity of natural killer cells and CD8 T cells in vivo. Without obvious side effects, (As + Ce6)@MSNs-PEG treatment significantly inhibited tumor growth and extended the lifespan of tumor-bearing mice. Further results revealed that treatment of (As + Ce6)@MSNs-PEG led to enhanced IFN secretion by immune cells and increased T-box transcription factor (T-bet), which is highly expressed by T cells. Therefore, (As + Ce6)@MSNs-PEG may serve as an effective and safe platform for combinatory use with nano-herb medicine and PDT to provide a new therapy for colon cancer treatment.
已经开发并使用了多种疗法来治疗结肠癌,然而,高死亡率仍然居高不下,更有效的治疗策略仍亟待开发。在这项研究中,我们开发了一种免疫疗法,该疗法由固有免疫激活剂黄芪甲苷 III(As)和光动力疗法(PDT)试剂氯 e6(Ce6)组成(As + Ce6)@MSNs-PEG,用于结肠癌的治疗。我们表明(As + Ce6)@MSNs-PEG 可以有效地激活 NK 细胞并抑制体外肿瘤细胞的增殖。它还可以有效地到达肿瘤部位,诱导免疫细胞浸润肿瘤,并增强体内自然杀伤细胞和 CD8 T 细胞的细胞毒性。(As + Ce6)@MSNs-PEG 治疗没有明显的副作用,显著抑制了肿瘤的生长并延长了荷瘤小鼠的寿命。进一步的结果表明,(As + Ce6)@MSNs-PEG 的治疗导致免疫细胞分泌 IFN 增加,T 细胞中高度表达的 T 盒转录因子(T-bet)增加。因此,(As + Ce6)@MSNs-PEG 可能作为一种有效的、安全的平台,与纳米草药药物和 PDT 联合使用,为结肠癌的治疗提供一种新的疗法。